Resistin-like molecule α decreases glucose tolerance during intestinal inflammation

Ariel Munitz, Luqman Seidu, Eric T. Cole, Richard Ahrens, Simon P. Hogan, Marc E. Rothenberg

Research output: Contribution to journalArticlepeer-review

Abstract

Resistin-like molecule α (Relm-α) is a secreted cysteine-rich protein belonging to a newly defined family of proteins, including resistin, Relm-β, and Relm-γ. Resistin was initially defined based on its insulin resistance activity, but the family members are highly up-regulated in various inflammatory states, especially those involving intestinal inflammation. In this study, we report the role of Relm-α at baseline and following an experimental model of colitis. Relm-α was readily detected in the serum at baseline (4-5 ng/ml), and its level was regulated by energy uptake. Retnla -/- mice had decreased baseline circulating leptin levels, but displayed normal glucose, glucose clearance, and insulin levels. Following exposure to the oral innate trigger dextran sodium sulfate (DSS), a nonredundant proinflammatory role for Relm-α was uncovered as Retnla-/- mice were markedly protected from DSS-induced disease activity and histopathological features. Relm-α regulated eosinophil-directed cytokines (e.g., IL-5, CCL11/eotaxin-1, and CCL5/RANTES) and IL-17 ex vivo. Consistently, DSS-treated Retnla-/- mice displayed substantially decreased eosinophil accumulation and decreased phosphorylation of NF-κB, ERK1/2, and p38 in macrophages and eosinophils. Following DSS exposure, serum level of Relm-α was up-regulated, and DSS-treated Retnla-/- mice were markedly protected from hyperglycemia induced by glucose injection independent of changes in insulin levels. Retnla-/- mice were protected from increases in gut hormone serum levels of gastric inhibitory polypeptide and peptide YY that were induced following DSS treatment. These findings demonstrate a central proinflammatory role for Relm-α in the regulation of colonic inflammation and a novel link between colonic injury, glucose tolerance, and energy intake.

Original languageEnglish
Pages (from-to)2357-2363
Number of pages7
JournalJournal of Immunology
Volume182
Issue number4
DOIs
StatePublished - 15 Feb 2009

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